The normal structure of the oral mucosa is maintained by continuous cell proliferation of the epithelium. For some other tissues, there is evidence that only a small fraction of the proliferative cells, stem cells, have the ability to divide indefinately. These cells are responsible for providing the differentiating cells during normal turnover and for regeneration of the tissue following wounding and radiation damage. They may have unusual patterns of differential division. Although it is probable that stem cells exist in oral mucosa, and have important implications for oral disease, they have not yet been clearly identified. Pilot experiments have indicated the presence of a small number of mucosal epithelial cells which have an atypically-long cell cycle and may be stem cells. The proposed research will employ techniques of light and electron microscopic autoradiography, histochemistry and cell culture in further studies of these cells in order to: a) examine their function as stem cells, b) to determine their number and distribution in relation to tissue architecture, c) to investigatate their rate of normal proliferation and patterns of division, and d) to investigate their "clonogenic" abilities. As it is postulated that stem cells play an important role in carcinogenesis, the response of these cells during induction of hyperplasia will be investigated.